Phase I Study of BMS-214662 and Paclitaxel in Patients With Advanced Malignancies

Trial Information

Phase I Study of BMS-214662 and Paclitaxel in Patients With Advanced Malignancies

OBJECTIVES: I. Determine the maximum tolerated dose of BMS-214662 in combination with paclitaxel in patients with advanced solid tumors. II. Determine the safety and tolerability of this regimen in these patients. III. Determine the pharmacokinetics of this treatment regimen in this patient population. IV. Determine the pharmacodynamic effects of this treatment regimen in serial tumor biopsies in these patients. V. Determine the cytotoxicity of this treatment regimen in these patients.

OUTLINE: This is a dose-escalation study of BMS-214662. Patients receive paclitaxel IV over 3 hours on day 1 and BMS-214662 IV over 1 hour on day 3 of course 1. For all subsequent courses, patients receive paclitaxel IV over 3 hours followed 30 minutes later by BMS-214662 IV over 1 hour on day 1. Treatment repeats every 3 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable disease or objectively responding disease receive additional therapy at the investigator's discretion. Cohorts of 3-6 patients receive escalating doses of BMS-214662 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Patients are followed every 4 weeks.

PROJECTED ACCRUAL: A maximum of 18-21 patients will be accrued for this study within 12-15 months.

Inclusion Criteria

DISEASE CHARACTERISTICS: Histologically or cytologically confirmed solid tumor unresponsive to standard therapy or for which no effective therapy exists Measurable or evaluable disease amenable to CT-guided or percutaneous needle biopsy No active symptomatic brain metastases requiring steroids, including evidence of cerebral edema on CT scan or MRI or progression from prior imaging study

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: At least 3 months Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.5 mg/dL ALT/AST no greater than 2.5 times upper limit of normal (ULN) Renal: Creatinine no greater than 1.5 times ULN Cardiovascular: No history of clinically significant cardiac arrhythmia that could be exacerbated by QT interval prolongation No uncontrolled or significant cardiovascular disease No myocardial infarction within the past 6 months No significant congestive heart failure No second- or third- degree heart block No prolonged QTc interval (greater than 450 ms) on EKG Pulmonary: No uncontrolled or significant pulmonary disease Other: No serious uncontrollable medical disorder or active infection that would preclude study No dementia or altered mental status that would preclude study Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception

Name

Location

We are a Cancer Social Network, Resource Directory & Education Hub supporting all those affected by cancer. knowcancer.com is intended to be solely for informational purposes and should not be a substitute for professional medical advice, diagnosis or treatment.